In vitro biocompatibility study of free and liposomaly-grafted copolymers bearing short blocks of aliphatic lipid-mimetic units Cytotoxicity and hemolytic activity

This study presents an evaluation of the cytotoxic properties and hemolytic potential of four copolymers bearing 1, 2 or 4 lipid-mimetic units, designed as surface modifying agents for liposomes, vs. the commercially available PEG-lipid DSPE-PEG2000. The biocompatibility of model liposomal formulations incorporating 5 mol% of chosen polymers was also investigated. The conducted MTT-assay and morphological observations indicate that the single lipid anchor-bearing copolymers DDP(EO)52 and DDP(EO)92 exert strong cytotoxicity against human cells (HL-60, OPM-2, MGH-U1 and HUVECs), whereas the 2 or 4 lipid anchor-bearing copolymers and DSPE-PEG2000 are devoid of cytotoxic effects. Among the liposomal formulations tested, cytotoxicity was encountered only when 5 mol% of DDP(EO)52 was incorporated. The hemolysis evaluation revealed that DDP(EO)52 (free and liposomal) and DDP(EO)92 significantly deteriorated the integrity of erythrocyte membranes after 72 h whereas the other tested polymers and liposomal formulations were non-hemolytic.